Field of Selenium Use in Humans
Selenium is a chemical element with atomic number 34 and chemical symbol “Se.” Selenium occurs rarely in the free-state in nature. It is a nonmetal that is chemically related to sulfur and tellurium. Although selenium is toxic in large amounts, it is considered an essential trace element and essential micro-nutrient for both animals and humans. Selenium is essential to form the active center of certain enzymes necessary for the function of all cells in both humans and animals. Selenium requirements in plants, animals and humans differ by species.
In humans, selenium is a trace element nutrient which functions as a cofactor for reduction of antioxidant enzymes such as glutathione peroxidases and thioredoxin reductase. However, ongoing research has identified that selenium has a physiological role involving enzymes in addition to the glutathione peroxidases. Selenium plays an important role in non-antioxidants' functions as well. For example, selenium also plays a role in the functioning of the thyroid gland by participating as a cofactor for thyroid hormone deiodinases. Selenium is also critical to immunocompetence as well as reproductive and other physiological functions of the body. However, the majority of research focuses on selenium's effectiveness as an antioxidant. Such protection is critical so that intracellular environments of all cells are protected from oxidants and allow enzymatic functions to protect the body.
Research focusing on the supplementation of human diets with selenium is a result of the finding that selenium is an essential trace element with numerous health benefits directly related to a person's dietary intake of selenium. Perhaps most importantly, selenium is a part of the antioxidant enzyme system in the body. Selenium works with other functional proteins in the body to ensure that toxic free radicals and peroxides formed intracellular remain neutralized to prevent cellular damage and numerous diseases, including cancers.
Despite this increase in evidence showing the importance of selenium in the human diet, it is apparent that humans are becoming increasingly selenium deficient. This is caused by a variety of factors, including the fact that soils in many regions where livestock are grown are either low in selenium content or selenium-deplete. As a result, crops grown in such soil have a lower selenium concentration and the animals that feed off of such crops are often selenium deficient. Ultimately, low selenium levels in crops and animals results in decreased selenium intake through animal products that humans consume.
Table 1 shows the impact of selenium contact in the soil and the resulting impact on cattle raised in these areas. Research has focused on how cattle raised on soils containing different levels of selenium can impact the levels found in the meat. It is concluded that high soil levels will increase the naturally occurring organic selenium levels in forage grown and be transferred to the animal.
TABLE 1IngredientDiet Se Level, mg/kgMuscle Se Level, mg/kgHintze et al. (2002)High area2.10Low area0.40High/low/0.621.20/0.35High/low/11.92.06/1.50
Such depletion of selenium and resultant decreased intake of selenium is significant as several studies have suggested a link between cancers in humans and selenium deficiencies. FIGS. 1-4 demonstrate the direct correlation between selenium levels in humans and types of cancer. This link between selenium content and various forms of cancer results from the association between neutrophils and other phagocytic cells and a human's selenium status. Additional, studies have shown that selenium is active in mammary glands against mastitis pathogens, is active in the lungs against respiratory pathogens, and is also active in utero against foreign bacteria, placental membranes postpartum and against other phagocytic cells in the body. (See Combs, American Society for Nutritional Sciences, 2005).
Studies on the effect of selenium supplementation related to the recurrence of skin cancers did not demonstrate a reduced rate of recurrence of skin cancers; however the results did show a significantly reduced occurrence of total cancers. (See L. C. Clarke et al. JAMA, 276:1957-1963, 1996). Clarke observed that approximately 200 mcg of selenium supplemented in a chemically organic form derived from selenium yeast are required per day to receive anticancer effects of the trace mineral. Additionally, dietary selenium has been shown to prevent chemically induced carcinogenesis in rodent studies.
Selenium may help prevent cancer by acting as an antioxidant or by enhancing immune activity. The Food and Drug Administration (“FDA”) also acknowledges the potential anticancer benefits of selenium by allowing the following claims to be made regarding selenium:
Claim 1:                “Selenium may reduce the risk of certain cancers. Some scientific evidence suggests that consumption of selenium may reduce the risk of certain forms of cancer. However, FDA has determined that this evidenced is limited and not conclusive.”        
Claim 2:                “Selenium may produce anticarcinogenic effects in the body. Some scientific evidence suggests that consumption of selenium may produce anticarcinogenic effects in the body. However, FDA has determined that this evidence is limited and not conclusive.”            (Health Claim Petition: Selenium and Reduced Risk of Certain Cancers and Selenium and Anticarcinogenic Effects (Docket No. 02P-0457)).
The treatment and prevention of cancer represent a significant public health concern within the United States and throughout the world. Cancer remains the second-leading cause of death within the United States alone. The American Cancer Society, Cancer Facts and Figures estimates that one of every four deaths in the United States is a result of cancer. Accordingly, there is an ongoing long-felt need in the public health community for cancer treatments and preventions, and to decrease one's risk of developing various forms of cancers.
Human consumption of selenium comes from a variety of sources, including nuts, milk, meat, fish, and eggs. More than 66% of selenium intake in American diets comes from meat, milk, and eggs. See Table 2 for percentages of total selenium intake in common food items.
TABLE 2Selenium Intake from Common FoodsFood% of Total Se IntakeMeats26Dairy22Eggs18Fish12Cereals16Vegetables, Nuts, etc.6
The most common form of selenium for human supplementation is selenomethionine. (Schrauzer, Feed Tech). Because animals and humans are unable to synthesize selenomethionine, virtually all selenium in animals and humans is obtained from the diet. In the United States, the recommended daily allowance (“RDA”) for adults is 55 micrograms per day. Most humans do not meet the RDA of selenium. Selenium supplementation is not common practice for most adults. Therefore, in order to reach the RDA a variety of selenium-rich sources of food must be consumed, including: organ meats and seafood (0.4-1.5 micrograms per gram); muscle meats (0.1-0.4 micrograms per gram); cereals and grains (less than 0.1 to greater than 0.8 micrograms per gram); dairy products (less than 0.1 to 0.3 micrograms per gram); and fruits and vegetables (less than 0.1 micrograms per gram). Of these sources of selenium in food products, meat and seafood are generally known to be more reliable sources of selenium, in comparison to plant products.
Ongoing health and nutrition studies show that dietary intake of selenium varies greatly among diverse populations. For example, a significant factor determining the intake of selenium from food and meats is the amount of meat a person intakes. The lowest selenium intakes are generally found in populations following vegetarian diets. Moreover, vegetarians living in areas where plants are grown in soil consisting of low selenium show even lower selenium intakes from their diet and are at an increased risk of becoming selenium deficient.
Clinical trials have shown that selenium's effectiveness as an antioxidant and anticancer agent is found at doses of approximately 200 micrograms per day. (See Clark et al.; Wellness Lifestyles, Inc., Petition to FDA for Health Plans Relating to Selenium and Reduction of Risk of Cancers).
In considering health claims allowable by the Food and Drug Administration, the agency recognized the lowest-observed adverse effect level of selenium intake as 900 micrograms per day and the no-observed adverse effect level of selenium as 800 micrograms per day. Therefore the FDA has taken a more conservative dosing schedule for selenium supplementation in concluding that 400 micrograms per day is the upper limit of selenium from food and supplements likely to pose no risk of adverse health effects in almost all people. As a result, the FDA concluded that the use of selenium as a dietary supplement at levels no greater than 400 micrograms per day was safe and lawful (taking into consideration an estimated 100 micrograms per day a person might consume from food sources).
Additional research is ongoing to determine the optimal levels of selenium and selenoproteins necessary to be beneficial for cancer and other diseases. (Rayman, Lancet, Vol. 356, 2000). Rayman's review article on the importance of selenium to human health cautions that a safe daily intake of selenium for human use is approximately 15 micrograms per kilogram body weight per day.
Field of Selenium Use in Bovine
Beef and other livestock animals are often given various forms of supplements in order to promote the animals' health and to achieve desirable meat products upon slaughter. Most often, supplementation with trace minerals, vitamins or other feed additives to livestock are formulated to provide the least expensive forms of supplementation to food animals. This generally results in animals being supplemented with the most inexpensive forms of trace minerals, which are the metallic or “inorganic” forms, such as oxides and sulfates. FIG. 7 shows the molecular structure of how selenium is typically supplemented in the form of sodium selenite. More importantly, FIG. 8 illustrates the molecular structure of organic L-selenomethionine. There are significant differences in bioavailability of trace minerals depending on the chemical form delivered. The relative bioavailability of sodium selenite in comparison to selenomethionine is 100 (baseline) and 245, respectively. See Table 3, according to Henry & Ammerman (1995).
TABLE 3SourceBioavailabilitySodium Selenite100Cobalt Selenite105Selenomethionine245Selenium Enriched Yeast290
Organic trace minerals, such as selenium, zinc, copper, manganese, and cobalt are a member of a large class of chemical compounds whose molecules contain carbon. There is often very low bioavailability of inorganic trace minerals to cross the gastrointestinal walls of food animals and still lower distribution in the blood stream and throughout the tissues of the animal. Such decreased distribution, absorption and bioavailability are generally a result of adhering to a least cost approach by animal producers as inorganic trace minerals are considerably less expensive. As a result, livestock mortality has been trending higher in the last 15 years. Loneragan et al. (J Am Vet Med Asso, 219:1122-1127 (2001)) showed mortality ratio increased from 10.3 deaths/1,000 cattle in 1994 to 14.2 deaths/1,000 cattle in 1999 which amounts to approximately 6.1% annual increase in mortality rate. (P=0.09). Respiratory disease or pneumonia has been increasingly implicated in the cause of increasing mortality. It is widely believed that depletions or deficiencies of various nutrients, including trace minerals, are compromising immunity in food animals, such as bovine.
Research relating to antioxidant use in animals through the supplementation of selenoproteins has shown a variety of improvements and benefits in an animal's health, performance and production. For example, selenoproteins have demonstrated improved immune response in neonatal livability, both male and female fertility, and decreased iron toxicity in neonates. However, such improvements in an animal's health, performance and production focus solely on the direct benefits to the animals supplemented with various forms of selenoproteins. These studies do not contemplate or suggest any beneficial effects as a result of human consumption of such supplemented animals' meat.
Beef, pork, and milk normally contain about 0.03 to about 0.06 ppm (mg/kg). However, the amounts of selenium required to obtain antioxidant and anticancer benefits in humans are significantly higher (from about 3-6 times greater) than the amounts which can be obtained by consuming reasonable amounts of cow's milk, beef, and pork. It is reasonable to say that cow's milk, beef, and pork while providing a large percentage of dietary selenium the human diet, does not contain enough selenium to provide the benefits of improved immune function, anticancer effects and other physiologic improvements. As a result, there is a need for selenium enhancement of meat products to be consumed by humans in order to provide beneficial antioxidants and anticancer effects when combined with the selenium consumed in the average human diet.
Supplementations for the purpose of improving an animal's health have traditionally utilized inorganic sources of selenium. However, data has demonstrated that organic selenium is less toxic than inorganic selenium. It has been shown that constant intakes in a nutritional range of selenium, through the supplementation of organic selenium, results in tissue selenium levels increasing until a steady state has been established, allowing effective supplementation while preventing the buildup to toxic levels. (Schrauzer, G. N., Selenomethionine: A Review of its Nutritional Significance, Metabolism and Toxicity, J. Nutr. 130:1653-1656). FIG. 5 shows the increased perfusion to various tissues of the animal, differing based on the administration of an organic versus an inorganic form. In all tissues, the organic selenium has the greatest concentration.
It is known that the selenium status of bovine can be increased by feeding only feedstuffs naturally high in selenium (i.e., organic form). The amount of selenium fed to bovine for purposes of supplementation or enhancement in food sources in directly correlated to the selenium content of the soil where such feed is grown. (See Wellness Lifestyles, Inc. Petition to FDA for Health Plans Related to Selenium and Reduction in the Risk of Cancers). Selenium enters a food chain through incorporation into plant proteins as amino acids L-selenocysteine and L-selenomethionine. However, there are only certain parts of North America where soil selenium is adequate enough to allow much uptake by plants grown for animal feed (including: North and South Dakota; Montana; and Alberta, Canada). See FIG. 10. It is generally accepted that most of the areas where food animals are produced in the United States have very little selenium left in the soils. Therefore, it is not practical in the United States to rely only on selenium in the feedstuffs (i.e., corn, hay, soybeans) to meet the minimum requirements.
Pavlata et al. have shown that oral administration of organic selenium results in higher tissue concentrations than intramuscular injection of inorganic selenium. See FIG. 6. However, such research is merely aimed at demonstrating the biological effects that trace elements have on animals' health and performance. For example, Pavlata et al. look to trace elements for feed additives as replacements for antibiotics and hormonal growth stimulants. The results show that long-term oral administrations of organic selenium resulted in higher blood selenium concentrations than intramuscular injection of an inorganic selenium-containing compound. See FIG. 5. Such therapies were tested and are intended to be used solely for treating selenium deficiencies in animals. As a result, those skilled in the art traditionally use inorganic selenium forms, such as sodium selenite, for use in premixes, supplements and complete feed products to be ultimately sold to producers to supplement selenium-deficient diets in animals, such as cattle. There is no focus or interest in the use of organic selenium sources to provide an enhanced diet for beef cattle for the purpose of supplementing the human diet for selenium deficiencies and the prevention of diseases such as cancer.
Some focus has been placed on organic sources of selenium. The fermentation of yeast is a source that can form organic selenium and can be used to supplement livestock feed. It would be advantageous and solve a long-felt problem in the art of human cancer prevention and therapy, and other human pathologies, to develop methods to enhance the diet of bovine through the use of organic selenium, such as fermented yeasts, to ultimately pass along for human consumption meat with enhanced selenium content.
There is, therefore, a pressing need for a new, safe, efficient and non-invasive method of administering to humans, bovine meat that is enhanced with selenium to not only meet the RDA, but also enhance one's selenium intake to receive the beneficial immune and anticancer effects of selenium.
Therefore, it would be advantageous to have a method of increasing the selenium content in beef.
It would also be advantageous to develop beef with increased content of other organic minerals, such as zinc, copper and manganese.